What is the first lab test to check in a neonate with elevated Thyroid Stimulating Hormone (TSH) levels?

First Lab Test in Neonatal Elevated TSH

When a neonate has an elevated TSH on newborn screening, the first confirmatory test to check is serum free T4 (or total T4), measured simultaneously with a venous TSH level to confirm the screening result and differentiate between subclinical and overt hypothyroidism. 1

Diagnostic Algorithm

Initial Confirmatory Testing

• Obtain venous blood for both TSH and free T4 (or total T4) simultaneously as soon as possible after a positive newborn screen 2, 3
• The combination of these two values determines the diagnosis and urgency of treatment:
  • Overt primary hypothyroidism: Elevated TSH + Low T4/free T4 → Requires immediate treatment 2, 3
  • Subclinical hypothyroidism: Elevated TSH + Normal T4/free T4 → Management depends on TSH level and clinical context 4
  • Transient hyperthyrotropinemia: Mildly elevated TSH that normalizes → May not require treatment 4

Why Free T4 Must Be Checked First

• TSH alone cannot distinguish between overt and subclinical hypothyroidism, which have vastly different treatment urgencies and long-term implications 2, 3
• Free T4 levels determine neurodevelopmental risk: Low T4 in the newborn period directly threatens brain development, while isolated TSH elevation with normal T4 carries much less risk 2, 5
• Treatment goals are T4-driven: The immediate therapeutic goal is to rapidly raise serum T4 above 130 nmol/L (10 μg/dL), not to normalize TSH 2, 3

Clinical Context and Timing

Timing Considerations

• Samples should be obtained after 24 hours of age to avoid false positives from the physiological TSH surge that occurs in the first 1-2 days after birth 5
• Early hospital discharge increases false positive rates, making confirmatory testing even more critical 5

Treatment Thresholds Based on Confirmatory Results

• TSH >20 mU/L with low free T4: Start levothyroxine 10-15 mcg/kg/day immediately 2, 3
• TSH 20-30 mU/L with normal free T4: Treatment decisions depend on age at testing, TSH trend, and absolute free T4 level (whether in upper or lower half of normal range) 4
• TSH >30 mU/L even with normal free T4: Generally warrants treatment 4

Common Pitfalls to Avoid

• Do not delay confirmatory testing: Infants with congenital hypothyroidism often appear normal at birth due to transplacental passage of maternal thyroid hormone, but delayed diagnosis causes irreversible mental retardation 2, 5
• Do not rely on clinical examination alone: Physical signs (myxedematous facies, macroglossia, umbilical hernia, hypotonia) are often subtle or absent in the newborn period 2
• Do not assume all TSH elevations are permanent: In iodine-deficient or iodine-excess regions, transient neonatal hyperthyrotropinemia is common and may not require treatment 4

Additional Diagnostic Tests (Secondary Priority)

After confirming the diagnosis with TSH and free T4, additional tests may help identify the etiology but should not delay treatment initiation 2, 3:

• Thyroid ultrasound or radionuclide scan to detect dysgenesis
• Serum thyroglobulin to distinguish athyreosis from ectopic tissue
• Maternal thyroid antibodies if transient antibody-mediated hypothyroidism is suspected